A Phase III Trial of Hypofractionated External Beam Image-Guided Highly Targeted Radiotherapy: The HEIGHT Trial (HEIGHT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by University of Miami
Sponsor:
Information provided by (Responsible Party):
Alan Pollack, University of Miami
ClinicalTrials.gov Identifier:
NCT01411332
First received: August 3, 2011
Last updated: August 3, 2016
Last verified: August 2016

August 3, 2011
August 3, 2016
May 2011
May 2017   (final data collection date for primary outcome measure)
Rate of prostate biopsy positivity in patients receiving HTIMRT versus patients receiving SIMRT at 2 years after all therapy. [ Time Frame: 2 years post-therapy ] [ Designated as safety issue: No ]
Rate of prostate biopsy positivity in HTIMRT patients versus SIMRT patients at 2 years after all therapy.
To compare the rate of prostate biopsy positivity after HTIMRT to SIMRT at 2 years after all therapy. [ Time Frame: 2 - 2.5 years post-therapy ] [ Designated as safety issue: No ]
The proportion of positive biopsy findings among patients without clinical or biochemical failure 2-2.5 years after completing study treatment (RT or ADT, whichever is longer).
Complete list of historical versions of study NCT01411332 on ClinicalTrials.gov Archive Site
  • Rate of acute and late toxicity in patients receiving HTIMRT. [ Time Frame: 5.25 years ] [ Designated as safety issue: Yes ]
    Rate of acute and late toxicity in patients receiving HTIMRT. Acute toxicity is defined as toxicity occurring during treatment and within three months of completing treatment. Late toxicity is defined as toxicity occurring more than three months after treatment completion.
  • Rate of influence of HTIMRT on patients' on quality of life. [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    Rate of influence of HTIMRT on patients' quality of life including health-related quality of life (HR-QOL), prostate cancer-specific anxiety and prostate cancer-specific QOL as measured by psychosocial questionnaires.
  • Quantification of biomarker expression in different prostate tumor regions. [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    Quantification biomarker expression in different prostate tumor regions, comparing specifically the functional MRI suspicious regions to those that are not suspicious.
  • Incidence and relationship of circulating free DNA and tumor cells to tissue biomarkers and prostate biopsy positivity. [ Time Frame: 2 years post-completion of therapy ] [ Designated as safety issue: No ]
    Incidence and relationship of circulating free DNA and tumor cells to tissue biomarkers and prostate biopsy positivity at 2 years after completion of protocol therapy.
  • Rate of Biochemical Failure, Clinical Failure and Failure-Free Survival (FFS) in Patients [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    Rate of biochemical failure and clinical failure in patients. Biochemical failure is defined as prostate-specific antigen (PSA) ≥ nadir + 2 ng/mL. Clinical failure is defined as at least local failure due to newly identified extension outside of the prostate after initial regression, or urinary obstructive symptoms with carcinoma found at transurethral resection of the prostate (TURP) or regional/distant failure due to radiographic evidence metastasis (nodal or hematogenous spread). Failure-Free Survival (FFS) is the elapsed time from start of radiotherapy to first documented evidence of biochemical or clinical failure or death from any cause, whichever occurs first. In the absence of any event defining failure, follow-up time will be censored at the date of last documented failure-free status.
  • Rate of Overall Survival (OS) [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    Mortality endpoint. Overall Survival (OS) is the elapsed time from start of radiotherapy to death from any cause. For surviving patients, follow-up will be censored at the date of last contact.
  • Number of patients with, and severity of, acute and late adverse events in an HT boost clinical trial. [ Time Frame: 5.25 years ] [ Designated as safety issue: Yes ]
    Number of patients with, and severity of, acute and late adverse events in an HT boost clinical trial.
  • To evaluate the influence of HTIMRT to health-related quality of life (HRQOL), prostate cancer-specific anxiety and prostate cancer-specific QOL. [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    Two contemporary instruments (questionnaires) will be utilized to assess patient function and bother (Expanded Prostate Cancer Index Composite-SF12 (EPIC-SF12) and the prostate cancer-specific anxiety Memorial Anxiety Scale for Prostate Cancer patients (MAX-PC).
  • To quantify biomarker expression in different prostate tumor regions, comparing specifically the DCE-MRI enhancing and non-enhancing regions. [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    Quantification of the amount of the biomarker specific immunohistochemical staining in the area of tumor.
  • To evaluate the incidence and relationship of circulating free DNA and tumor cells to tissue biomarkers and prostate biopsy positivity at 2 years after completion of therapy. [ Time Frame: 2 years post-completion of therapy ] [ Designated as safety issue: No ]
    The investigators test whether absolute pretreatment CTC counts and treatment-induced changes in CTC counts as assessed on our novel microfilter platform correlate with response to therapy (biopsy positivity at two years after treatment).
  • Biochemical failure or clinical failure [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    The cumulative incidence of biochemical or clinical failure allowing for competing risk as needed. Clinical failure is defined as at least a 25% increase in the size of the tumor relative to the smallest volume recorded, or new extension of tumor beyond the capsule, or re-extension of tumor beyond the capsule after initial regression, or urinary obstructive symptoms with carcinoma found at TURP. Biochemical failure is defined as PSA ≥ nadir + 2 ng/mL.
  • Failure-free Survival (FFS) [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    The elapsed time from start of radiotherapy to first documented evidence of biochemical or clinical failure or death from any cause, whichever occurs first. In the absence of any event defining failure, follow-up time will be censored at the date of last documented failure-free status.
  • Overall Survival (OS) [ Time Frame: 5.25 years ] [ Designated as safety issue: No ]
    The elapsed time from start of radiotherapy to death from any cause. For surviving patients, follow-up will be censored at the date of last contact.
Not Provided
Not Provided
 
A Phase III Trial of Hypofractionated External Beam Image-Guided Highly Targeted Radiotherapy: The HEIGHT Trial
A Phase III Trial of Hypofractionated External Beam Image-Guided Highly Targeted Radiotherapy: The HEIGHT Trial
  1. Delivery of directed hypofractionated targeted (HT) radiotherapy (RT) tumor boost to the dominant tumor lesion in the prostate as identified by multiparametric MRI will increase tumor eradication from the prostate.
  2. Biomarker expression levels differ in the multiparametric MRI defined regions at high risk of harboring tumors that determine outcome.
  3. 10-15% of men undergoing RT have Circulating DNA or tumor cells (CTC) that are related to an adverse treatment outcome.
  4. Quality of life will not differ significantly between the treatment arms.
  5. Prostate cancer-related anxiety will be reduced in the HTIMRT arm, because the patients will be aware that the dominant tumor will be targeted with higher radiation dose.
Not Provided
Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Prostate Cancer
  • Prostate Adenocarcinoma
  • Radiation: SIMRT
    A total dose of 80 Gy will be delivered in 40 fractions to the Clinical Target Volume (CTV).
    Other Name: Standard Fractionated Intensity Modulated Radiotherapy
  • Radiation: HTIMRT
    Dose escalation to the Multiparametric MRI (MP-MRI) by dose painting at 2.35-2.40 Gy per fraction, while the rest of the Clinical Target Volume (CTV) receives 2.0 Gy a fraction to 76 Gy. The hypofractionated targeted (HT) boost region will receive an absolute dose of 89.3-91.2 Gy. Assuming an α/β ratio of 3.0, this would be equivalent to 95.5 Gy in 2.0 Gy fractions.
    Other Name: Hypofractionated Targeted Intensity Modulated Radiotherapy
  • Behavioral: EPIC SF-12 Questionnaire
    Expanded Prostate Cancer Index Composite-Short Form 12 (SF12) (EPICSF-SF12) quality of life questionnaire prior to, during and post radiation therapy per protocol.
  • Behavioral: MAX-PC Questionnaire
    Memorial Anxiety Scale for Prostate Cancer patients (MAX-PC) questionnaire prior to, during and post radiation therapy per protocol.
  • Behavioral: IPSS Questionnaire
    International Prostate Symptom Score (IPSS) questionnaire prior to, during and post radiation therapy per protocol.
  • Active Comparator: Arm I: SIMRT
    Arm I: Standard Fractionated Intensity Modulated Radiotherapy (SIMRT), EPIC SF-12 Questionnaire, MAX-PC Questionnaire, IPSS Questionnaire
    Interventions:
    • Radiation: SIMRT
    • Behavioral: EPIC SF-12 Questionnaire
    • Behavioral: MAX-PC Questionnaire
    • Behavioral: IPSS Questionnaire
  • Active Comparator: Arm II: HTIMRT
    Arm II: Hypofractionated Targeted Intensity Modulated Radiotherapy (HTIMRT), EPIC SF-12 Questionnaire, MAX-PC Questionnaire, IPSS Questionnaire
    Interventions:
    • Radiation: HTIMRT
    • Behavioral: EPIC SF-12 Questionnaire
    • Behavioral: MAX-PC Questionnaire
    • Behavioral: IPSS Questionnaire
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
72
May 2017
May 2017   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • A. Biopsy confirmed adenocarcinoma of the prostate.
  • B. T1-T3a disease based on digital rectal exam.

    1. T1a is permitted if peripheral zone biopsies are positive.
    2. T3a disease based on MRI is acceptable.
  • C. No evidence of metastasis by any clinical criteria or available radiographic tests.
  • D. Gleason score 6-8.
  • E. Patients with Gleason score 8 must be offered long term androgen deprivation therapy (ADT) and refuse such treatment because only 4-6 (±2 months) months (short term ADT) is permitted on this protocol. Gleason score ≥ 8 patients should be recommended to receive short term ADT in conjunction with RT. When given, the ADT recommended to begin after fiducial marker placement, if applicable; however, ADT is permitted to have been started up to two months prior to the signing of consent.

    1. Patients with Gleason score 8 disease must have <40 of the diagnostic tumor tissue involved with tumor.
    2. Patients with Gleason score ≤7 may be treated with 4-6 (±2 months) months of ADT.
  • F. PSA ≤100 ng/mL within 3 months of enrollment. If PSA was above 100 and dropped to ≤100 with antibiotics, this is acceptable for enrollment.
  • G. If PSA is >15 ng/ml or there is ≥ Gleason 8 disease, a bone scan should be obtained ≤4 months before enrollment and should be without evidence of metastasis. A questionable bone scan is acceptable if plain x-rays, CT and/or MRI are negative for metastasis.
  • H. No previous pelvic radiotherapy
  • I. No previous history of radical/total prostatectomy (suprapubic prostatectomy is acceptable)
  • J. No concurrent, active malignancy, other than nonmetastatic skin cancer or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for ≥ 5 years then the patient is eligible.
  • K. Identifiable multiparameter functional MRI defined tumor lesion or lesions using a 1.5T or 3.0T MRI (3.0T preferable), that total in volume <33% of the prostate within 3 months prior to enrollment.

    a. Multiparametric functional including diffusion weighted imaging (DWI) of prostate and pelvis is required prior to protocol consideration

  • L. Ability to understand and the willingness to sign a written informed consent document
  • M. Zubrod performance status <2 (Karnofsky or Eastern Cooperative Oncology Group (ECOG) performance status may be used to estimate Zubrod)
  • N. Willingness to fill out quality of life/psychosocial forms.
  • O. Age ≥35 and ≤85 years.
  • P. Serum testosterone is within 40% of normal assay limits (e.g., x=0.4*lower assay limit and x=.04*upper assay limit + upper assay limit),, taken within 4 months of enrollment. Patients who have been started on ADT prior to signing consent are not required to have a serum testosterone at this level prior to signing consent; but, a serum testosterone prior to fiducial marker placement is recommended.
  • Q. Serum liver function tests (LFTs) taken within 3 months of enrollment.
  • R. Complete blood counts taken within 3 months of enrollment.

Exclusion Criteria

  • A. Previous pelvic radiotherapy.
  • B. Previous history of radical prostatectomy.
  • C. Concurrent, active malignancy, which is not nonmetastatic skin cancer or early stage chronic lymphocytic leukemia (well-differentiated small cell lymphocytic lymphoma). If a prior malignancy is in remission for < 5 years then the patient is not eligible
  • D. Not willing to fill out quality of life/psychosocial questionnaires.
Male
35 Years to 85 Years   (Adult, Senior)
No
United States
 
NCT01411332
20100635
Yes
Yes
Some data after completion of the trial and publication of the primary endpoint. Additional data after publication of the secondary endpoints.
Alan Pollack, University of Miami
University of Miami
Not Provided
Principal Investigator: Alan Pollack, MD, PhD University of Miami
University of Miami
August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP